Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci

Kooner, J S and Saleheen, Danish and Sim, Xueling and Sehmi, Joban and Zhang, Weihua and Frossard, Philippe and Been, Latonya F and Chia, Kee-Seng and Dimas, Antigone S and Hassanali, Neelam and Jafar, Tazeen and Jowett, Jeremy B M and Li, Xinzhong and Radha, V and Rees, Simon D and Takeuchi, Fumihiko and Young, Robin and Aung, Tin and Basit, Abdul and Chidambaram, M and Das, Debashish and Grundberg, Elin and Hedman, Å K and Hydrie, Z I and Islam, M and Khor, Chiea-Chuen and Kowlessur, S and Kristensen, M M and Liju, S and Lim, Wei-Yen and Matthews, D R and Liu, J and Morris, A P and Nica, A C and Pinidiyapathirage, J M and Prokopenko, I and Rasheed, A and Samuel, M and Shah, N and Shera, A S and Small, K S and Suo, C and Wickremasinghe, A R and Wong, T Y and Yang, M and Zhang, F and Abecasis, G R and Barnett, A H and Caulfield, M and Deloukas, P and Frayling, T M and Froguel, P and Kato, N and Katulanda, P and Kelly, M A and Liang, J and Mohan, V and Sanghera, D K and Scott, J and Seielstad, M and Zimmet, P Z and Elliott, P and Teo, Y Y and McCarthy, M I and Danesh, J and Tai, E S and Chambers, J C (2011) Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci. Nature Genetics, 43 (10). p. 984. ISSN 1061-4036

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We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 1 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 1 10−4 for testing in a replication sample of 1 13,170 cases and 25,398 controls, also all of South Asian ancestry. In the combined analysis, we identified common genetic variants at six loci (GRB14, ST6GAL1, VPS26A, HMG20A, AP3S2 and HNF4A) newly associated with T2D (P = 4.1 1 × 1 10−8 to P = 1 1.9 × 1 10−1111). SNPs at GRB14 were also associated with insulin sensitivity (P = 5.0 × 1 10−4), and SNPs at ST6GAL1 and HNF4A were also associated with pancreatic beta-cell function (P = 0.02 and P = 0.001, respectively). Our findings provide additional insight into mechanisms underlying T2D and show the potential for new discovery from genetic association studies in South Asians, a population with increased susceptibility to T2D.

Item Type:Article
Official URL/DOI:
Uncontrolled Keywords:T2DM;South Asian;Genome-wide
Subjects:Genetics and Diabetes
Divisions:Neonatal Diabetes
Department of Diabetology
ID Code:598
Deposited On:03 Nov 2011 12:06
Last Modified:03 Nov 2011 12:06

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